Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.

BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics. CONCLUSIONS: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR.

[MELALIB 15: A retrospective observational study of 383 cases of melanoma diagnosed by dermatologists in private practice]. / MELALIB15 : étude observationnelle rétrospective de 383 mélanomes dépistés par des dermatologues libéraux.

BACKGROUND: Early detection of melanoma constitutes a major challenge and is a common reason for dermatological consultations. There is no recent data on melanomas diagnosed in the private medical sector in France, nor on the circumstances of diagnosis. PATIENTS AND METHODS: This was a retrospective observational study on records collating data on all new consecutive cases of melanoma diagnosed between January 2015 and June 2018, in the private sector only, by volunteer dermatologists belonging to the association for continuing medical education, "Dermatologie Paris XV". A data collection sheet was prepared on which to record information about the dermatologist, the patient, the main complaint, the characteristics of the melanoma, and the initial treatment given, using the computerized list provided by our dermatopathology offices. RESULTS: The study involved 383 cases of melanoma, 37% in situ and 63% invasive, which consisted chiefly of superficial spreading melanoma. The median age of the cohort was 61 years and patients were predominantly female (58%). Follow-up of high-risk patients and complete routine examination (in those consulting for another reason) resulted in direct detection by a dermatologist of 202 of the 383 melanomas (52.7%); these melanomas had a lower median Breslow index than the rest of the cohort and were thin in the main. When patients consulted for a suspect lesion (139 cases), the lesion had been identified mostly by either the patient or by a relative (61% of cases). The decision to consult was made chiefly by the patients themselves, and the Breslow index was thicker. An initial consultation for nevus screening resulted in diagnosis of 42 melanomas, i.e. only 11% of the cohort. Dermoscopy was performed by 92% of the dermatologists participating in the study. Melanoma excision was performed in the office by the practitioner in 75% of cases, and management was validated at multidisciplinary meetings in 65% of cases. CONCLUSION: In terms of French primary care, dermatologists in private practice play a key role in ensuring early detection and initial management of melanoma.

Renal haemodynamic response to amino acids infusion in an experimental porcine model of septic shock.

BACKGROUND: Acute kidney injury (AKI) is common in sepsis. Treatments allowing maintenance of renal blood flow (RBF) could help to prevent AKI associated with renal hypoperfusion. Amino acids (AA) have been associated with an increase of RBF and glomerular filtration rate (GFR) in several species. The aim of this study was to evaluate the effects of an AA infusion on RBF and GFR in a porcine model of septic shock. METHODS: A total of 17 piglets were randomly assigned into three groups: Sham (Sham, n = 5), sepsis without AA (S-NAA, n = 6), sepsis treated with AA (S-AA, n = 6). Piglets preparation included the placement of ultrasonic transit time flow probes around left renal artery for continuous RBF measurement; ureteral catheters for GFR and urine output evaluation; pulmonary artery catheter for cardiac output (CO) and pulmonary arterial pressure measurements. Mean arterial pressure (MAP) and renal vascular resistance (RVR) were also determined. Septic shock was induced with a live Pseudomonas aeruginosa infusion. Crystalloids, colloids and epinephrine infusion were used to maintain and restore MAP > 60 mmHg and CO > 80% from baseline. RESULTS: Renal haemodynamic did not change significantly in the Sham group, whereas RBF increased slightly in the S-NAA group. Conversely, a significant increase in RVR and a decrease in RBF and GFR were observed in the S-AA group. AA infusion was associated with a higher requirement of epinephrine [340.0 (141.2; 542.5) mg vs. 32.5 (3.8; 65.0) mg in the S-NAA group P = 0.044]. CONCLUSION: An infusion of amino acids impaired renal haemodynamics in this experimental model of septic shock.

Ankle brachial index using an automatic blood pressure device in occupational medicine: relevance in routine examination and comparison with Framingham cardio-vascular risk score.

AIM: The aim of this study was to assess the feasibility and relevance of determining ankle brachial index (ABI) using an automatic blood pressure device in subjects seen for their annual routine examination by occupational physicians and to compare the obtained ABI with the Framingham score. PATIENTS AND METHODS: Sixteen physicians randomly recruited 634 subjects in 12 departments of occupational medicine. Subjects aged between 40 and 60 years underwent a determination of ABI using an OMRON HM 722 device and the analysis of Framingham score. Other analysed variables were: sex, age, smoking habit, hypertension, diabetes, hypercholesterolemia, glycaemia, total cholesterol, HDL and LDL cholesterol and triglycerides levels. RESULTS: Mean age of the population studied was 48.1 ± 6.0 years; 73% were men, 36% were smokers, 14% had hypertension, 3.3% diabetes and 22% hypercholesterolemia. Biochemical values were glycaemia 0.90 ± 0.30 g/l, total cholesterol 2.10 ± 0.4 g/l, HDL cholesterol level 0.50 ± 0.20 g/l, LDL cholesterol level 1.30 ± 0.40 g/l, and triglycerides 1.40 ± 1.0 g/l. Mean ABI were 1.1 ± 0.1 in both legs. Mean Framingham score was 8.2 ± 5.4%. Only 20 subjects (3%) had an ABI < 0.90. No relation was found between pathological ABI and Framingham score (abnormal ABI : 9.9 ± 5.5 vs. normal ABI : 8.2 ± 5.4, NS). CONCLUSION: The determination of ABI using a simple commercially available automatic blood pressure device is feasible and easy to implement by preventive or general physicians in all kinds of routine examinations. In our opinion automatic ABI very easy and quick to determine provides, in addition to Framingham score, a simple and useful tool to detect subjects at high cardio-vascular risk.

A human metapneumovirus outbreak at a community hospital in England, July to September 2010.

We describe an outbreak of human metapneumovirus (hMPV) which occurred in July-September 2010 at a community hospital in the East of England. Based on the medical and nursing records, cases were retrospectively defined as suspected if they had had an influenza-like illness (ILI), and probable if they had had an ILI and an epidemiological link to a laboratory-confirmed case. Of a total of 17 symptomatic inpatients, five were classified as probable cases, five were laboratory confirmed and seven were suspected. The attack rate was 29.4% for confirmed and probable cases combined. The median age of symptomatic inpatients was 85 years-old (range 68-96) and the majority (16/17) of symptomatic inpatients had an underlying medical condition. Control measures introduced appeared to restrict further exposure of susceptible patients to infection although modelling suggested that up to four of 10 confirmed and probable cases (40%) could have been prevented through more timely diagnosis and recognition of an outbreak. These findings suggest that there should be increased awareness of hMPV infection within healthcare settings, particularly when the population at risk has a high prevalence of underlying co-morbidities.

Synthesis and characterization of pillared stevensites: application to chromate adsorption.

The purpose of this work was to study the synthesis of pillared interlayered clays from Moroccan stevensite called locally 'Ghassoul'. This clay has been intercalated with cetyltrimethylammonium surfactant (CTA-Stv) and aluminium hydroxypolycation (Al13-Stv). Characterization studies were performed using XRF, XRD, FTIR and DTA/TG analysis. Basal spacing values of Al13-Stv and CTA-Stv increased respectively from 13.5 A for natural stevensite to 17.5 and 17.6 A with increasing Al13(7+)/clay and CTA+/clay ratios. The DTA/TG results showed that Al13-Stv has a relatively high thermal stability compared with CTA-Stv. A quasi-irreversible intercalation by exchanging the interlayer inorganic cations with voluminous pillars Al13(7+) or CTA+ was observed. Batch adsorption of chromate anions from aqueous solutions was investigated and the results showed that both pillared clays had great affinity for the chromate compared with untreated stevensite. The Dubinin-Kaganer-Radushkevich (DKR) model was selected to describe the adsorption isotherms. The maximum adsorption capacities for natural stevensite, Al13-Stv and CTA-Stv are 13.7, 75.4 and 195.6 mmol/kg, respectively.

[Sleeping Sickness: A Cause of False Positive HIV Rapid Diagnostic Tests]. / Maladie du Sommeil: Une Cause de Faux Positifs des Tests de Diagnostic Rapide du VIH.

Approaching the mechanisms related to false positives HIV rapid diagnostic tests (RDT) in patients with sleeping sickness may help to improve the accuracy of screening for HIV infection in areas endemic for Human African trypanosomiasis (HAT).We report on a patient from Congo who was managed like an AIDS-associated meningoencephalitis, based on a false positive HIV RDT at admission, and eventually received a diagnosis of sleeping sickness. A further retrospective cohort study performed in patients with HAT shows that most of positive HIV RDT obtained prior to treatment for sleeping sickness are false positives. We found that half of them were cleared at the end of treatment course, suggesting an early clearance of some antibodies involved in cross-reactivity.A substantial clearance of HIV RDT false positives occurs during therapy for HAT. In areas where Elisa HIV tests are not readily available, repeating the HIV RDT at the end of therapy may help to identify roughly half of false positives.

Chemical characterization of Titan's tholins: solubility, morphology and molecular structure revisited.

In this work Titan's atmospheric chemistry is simulated using a capacitively coupled plasma radio frequency discharge in a N(2)-CH(4) stationnary flux. Samples of Titan's tholins are produced in gaseous mixtures containing either 2 or 10% methane before the plasma discharge, covering the methane concentration range measured in Titan's atmosphere. We study their solubility and associated morphology, their infrared spectroscopy signature and the mass distribution of the soluble fraction by mass spectrometry. An important result is to highlight that the previous Titan's tholin solubility studies are inappropriate to fully characterize such a heterogeneous organic matter and we develop a new protocol to evaluate quantitatively tholins solubility. We find that tholins contain up to 35% in mass of molecules soluble in methanol, attached to a hardly insoluble fraction. Methanol is then chosen as a discriminating solvent to characterize the differences between soluble and insoluble species constituting the bulk tholins. No significant morphological change of shape or surface feature is derived from scanning electron microscopy after the extraction of the soluble fraction. This observation suggests a solid structure despite an important porosity of the grains. Infrared spectroscopy is recorded for both fractions. The IR spectra of the bulk, soluble, and insoluble tholins fractions are found to be very similar and reveal identical chemical signatures of nitrogen bearing functions and aliphatic groups. This result confirms that the chemical information collected when analyzing only the soluble fraction provides a valuable insight representative of the bulk material. The soluble fraction is ionized with an atmospheric pressure photoionization source and analyzed by a hybrid mass spectrometer. The congested mass spectra with one peak at every mass unit between 50 and 800 u confirm that the soluble fraction contains a complex mixture of organic molecules. The broad distribution, however, exhibits a regular pattern of mass clusters. Tandem collision induced dissociation analysis is performed in the negative ion mode to retrieve structural information. It reveals that (i) the molecules are ended by methyl, amine and cyanide groups, (ii) a 27 u neutral moiety (most probably HCN) is often released in the fragmentation of tholin anions, and (iii) an ubiquitous ionic fragment at m/z 66 is found in all tandem spectra. A tentative structure is proposed for this negative ion.

Prospective pilot study for evaluation of high-flow oxygen therapy in dyspnoeic dogs: the HOT-DOG study.

OBJECTIVES: To describe the use, effectiveness and tolerance of high-flow oxygen therapy in dyspnoeic dogs. MATERIALS AND METHODS: Prospectively, dogs in acute respiratory distress admitted to an intensive care unit between January and May 2018 that failed to respond to nasal oxygen therapy and medical stabilisation after 30 minutes were transitioned to high-flow oxygen therapy. High-flow oxygen therapy, delivered an inspired oxygen fraction of 100% using an air/oxygen blender, active humidifier, single warmed tube and specific nasal cannula. Respiratory rate, pulse oximetry (SpO2 ), heart rate and a tolerance score were assessed every 15 minutes from T0 (under nasal oxygen) to 1 hour (T60 ), and PaO2 and PaCO2 at T0 and T60 . Complications were recorded for each dog. RESULTS: Eleven dogs were included. At T60 , PaO2 , flow rate and SpO2 were significantly greater than at T0 (171 ± 123 versus 73 ± 24 mmHg; P=0.015; 18 ±12 L/minute versus 3.2 ± 2.0 L/minute, P<0.01; 97.7 ±2.3% versus 91.6 ±7.2%, P=0.03, respectively). There was no significant difference in PaCO2 , respiratory rate or heart rate between T0 and T60 . Tolerance was excellent, and there were no complications. CLINICAL SIGNIFICANCE: High-flow oxygen therapy improves markers of oxygenation in dyspnoeic dogs and is an effective means to deliver oxygen with comfort and minimal complications.

Application of TMAH thermochemolysis to the detection of nucleobases: Application to the MOMA and SAM space experiment.

Thermochemolysis of seven nucleobases-adenine, thymine, uracil, cytosine, guanine, xanthine, and hypoxanthine-in tetramethylammonium hydroxide (TMAH) was studied individually by pyrolysis gas chromatography mass spectrometry in the frame of the Mars surface exploration. The analyses were performed under conditions relevant to the Sample Analysis at Mars (SAM) instrument of the Mars Curiosity Rover and the Mars Organic Molecule Analyzer (MOMA) instrument of the ExoMars Rover. The thermochemolysis products of each nucleobase were identified and the reaction mechanisms studied. The thermochemolysis temperature was optimized and the limit of detection and quantification of each nucleobase were also investigated. Results indicate that 600°C is the optimal thermochemolysis temperature for all seven nucleobases. The methylated products trimethyl-adenine, 1, 3-dimethyl-thymine, 1, 3-dimethyl-uracil, trimethyl-cytosine, 1, 3, 7-trimethyl-xanthine (caffeine), and dimethyl-hypoxanthine, respectively, are the most stable forms of adenine, thymine, uracil, cytosine, guanine, and xanthine, and hypoxanthine in TMAH solutions. The limits of detection for adenine, thymine, and uracil were 0.075 nmol; the limits of detection for guanine, cytosine, and hypoxanthine were higher, at 0.40, 0.55, and 0.75 nmol, respectively. These experiments allowed to well constrain the analytical capabilities of the thermochemolysis experiments that will be performed on Mars to detect nucleobases.

Stepped horn actuated Kelvin probe.

We have developed an original Kelvin probe system using an ultrasonic stepped horn sonotrode. This actuator is optimized in order to maximize the velocity of the tip end, and hence to increase the Kelvin current detected. Such development is essential to improve surface potential measurements at small spatial scale.

Toxicity assessment of the herbicides sulcotrione and mesotrione toward two reference environmental microorganisms: Tetrahymena pyriformis and Vibrio fischeri.

The potential toxicity of sulcotrione (2-[2-chloro-4-(methylsulfonyl)benzoyl]-1,3-cyclohexanedione) and mesotrione (2-[4-(methylsulfonyl)-2-nitrobenzoyl]-1,3-cyclohexanedione), two selective triketonic herbicides, was assessed using representative environmental microorganisms frequently used in ecotoxicology: the eukaryote Tetrahymena pyriformis and the prokaryote Vibrio fischeri. The aims were also to evaluate the toxicity of different known degradation products, to compare the toxicity of these herbicides with that of atrazine, and to assess the toxicity of the commercial herbicidal products Mikado and Callisto. Toxicity assays involved the Microtox test, the T. pyriformis population growth impairment test, and the T. pyriformis nonspecific esterase activity test. For each compound, we report original data (IC(50) values) on nontarget cells frequently used in ecotoxicology. Analytical standards sulcotrione and mesotrione showed no toxic effect on T. pyriformis population growth but a toxic influence was observed on nonspecific esterase activities of this microorganism and on metabolism of V. fischeri. Most of the degradation products studied and the two commercial formulations showed a greater toxicity than the parent molecules. Compared with the effect of atrazine, the toxicity of these triketonic herbicides was less than in T. pyriformis and greater than or the same as in V. fischeri. Additional work is needed to obtain a more accurate picture of the environmental impact of these herbicides. It will be necessary in future experiments to study the ecosystemic levels (aquatic and soil compartments) and to assess the potential toxicity of the newly discovered degradation products and of the additives accompanying the active ingredient in the commercial herbicidal formulations.

Nascent teichoic acids insertion into the cell wall directs the localization and activity of the major pneumococcal autolysin LytA.

The bacterial cell wall is in part composed of the peptidoglycan (PG) layer that maintains the cell shape and sustains the basic cellular processes of growth and division. The cell wall of Gram-positive bacteria also carries teichoic acids (TAs). In this work, we investigated how TAs contribute to the structuration of the PG network through the modulation of PG hydrolytic enzymes in the context of the Gram-positive Streptococcus pneumoniae bacterium. Pneumococcal TAs are decorated by phosphorylcholine residues which serve as anchors for the Choline-Binding Proteins, some of them acting as PG hydrolases, like the major autolysin LytA. Their binding is non covalent and reversible, a property that allows easy manipulation of the system. In this work, we show that the release of LytA occurs independently from its amidase activity. Furthermore, LytA fused to GFP was expressed in pneumococcal cells and showed different localization patterns according to the growth phase. Importantly, we demonstrate that TAs modulate the enzymatic activity of LytA since a low level of TAs present at the cell surface triggers LytA sensitivity in growing pneumococcal cells. We previously developed a method to label nascent TAs in live cells revealing that the insertion of TAs into the cell wall occurs at the mid-cell. In conclusion, we demonstrate that nascent TAs inserted in the cell wall at the division site are the specific receptors of LytA, tuning in this way the positioning of LytA at the appropriate place at the cell surface.

[Acute stent thrombosis due to resistance to clopidogrel ? A case report]. / Implication de la résistance au clopidogrel dans la thrombose aiguë de stent ? A propos d'un cas.

The authors report the case of a 65 year old man who presented with an acute coronary syndrome without ST elevation due to acute stent thrombosis 12 hours after implantation. Recent reports in the literature suggest the role of resistance to antiplatelet drugs in acute, subacute or late stent thrombosis. This patient was included in a protocol studying the response to antiplatelet drugs in patients undergoing coronary stenting and fulfilled the criteria of resistance to clopidogrel. This clinical case illustrates the possible role of "resistance" to antiplatelet drugs in stent thromboses.

Autocatalytic association of proteins by covalent bond formation: a Bio Molecular Welding toolbox derived from a bacterial adhesin.

Unusual intramolecular cross-links present in adhesins from Gram-positive bacteria have been used to develop a generic process amenable to biotechnology applications. Based on the crystal structure of RrgA, the Streptococcus pneumoniae pilus adhesin, we provide evidence that two engineered protein fragments retain their ability to associate covalently with high specificity, in vivo and in vitro, once isolated from the parent protein. We determined the optimal conditions for the assembly of the complex and we solved its crystal structure at 2 Å. Furthermore, we demonstrate biotechnological applications related to antibody production, nanoassembly and cell-surface labeling based on this process we named Bio Molecular Welding.

Specific and spatial labeling of choline-containing teichoic acids in Streptococcus pneumoniae by click chemistry.

Propargyl-choline was efficiently incorporated into teichoic acid (TA) polymers on the surface of Streptococcus pneumoniae. The introduction of a fluorophore by click chemistry enabled sufficient labeling of the pneumococcus, as well as its specific detection when mixed with other bacterial species. The labeling is localized at the septal site, suggesting a similar location of the TA and peptidoglycan (PG) synthetic machineries. This method is a unique opportunity to improve our understanding of the spatial location of pneumococcal TA biosynthesis.